Optical imaging is rapidly becoming one of the most versatile imaging modalities in biomedical research. The advantages of optical imaging compared to other imaging modalities include its non-ionizing low-energy radiation, high sensitivity for detecting objects in the micron range, and continuous data acquisition in real time and in an intact environment. The cost, space, and time demands associated with optical imaging are less than for other imaging modalities, and the speed and relative ease of imaging makes this modality attractive for potential clinical applications. The Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital (MGH) strives to develop and apply breakthrough imaging approaches in clinically meaningful ways. Our continuing success relies on the integration of new and emerging technologies into our existing research imaging repertoire, which includes functional and high-resolution magnetic resonance imaging (fMRI and MRI), magnetoencephalography (MEG), positron emission tomography (PET), and homebuilt functional optical imaging instrumentation. New technologies enhance our ability to validate and interpret data from our existing imaging resources and to combine imaging modalities for novel multimodal imaging applications-capabilities that are particularly needed in the emerging field of molecular imaging. We propose to purchase a state-of-the-art optical imaging system capable of 3D molecular imaging in transmission fluorescence, reflectance fluorescence, and bioluminescence modes in vivo, ex vivo, and in vitro. Significant advantages of the optical techniques possible with this system include the potential for multichannel imaging by using multiple probes with different spectral characteristics;quick, easy, and relatively low-cost rapid testing of biological hypotheses and proofs of principle in living experimental models. Importantly, optical bioluminescence imaging has unique advantages for detection of very low levels of signal because of its virtually background-free light emission. With its ease of operation, short acquisition time (typically 10-60 sec), and potential high-throughput format in vitro (microplates) and in vivo (5 mice, 23 cm FOV), this innovative system also provides high-throughput imaging capabilities. The new optical system will be an important resource for many currently funded biomedical imaging research projects. Major projects include studies on neurodenenerative disorders and brain function, cancer, and pancreatic islets in diabetes and transplantation. With the new in vivo optical imaging system and our existing imaging facilities under one roof, we can feasibly perform in-vivo experiments using one or more imaging modalities in succession, or even in parallel. This system will be an invaluable resource for the rich body of interdisciplinary research at the Martinos center and the larger MGH research community, as well as at other institutions in the greater Boston area. PUBLIC HEALTH RELEVANCE: Acquiring of a state-of-the-art in vivo optical imaging system with fluorescence and bioluminescence capabilities will allow for fast, easy and cheap ways to rapidly test biological hypotheses and proofs of principle in living experimental models, which could be further utilized for in vivo drug screening, development of imaging reporters and versatile animal studies in cancer, neurological disorders, diabetes and cardiovascular pathologies.